Alpelisib, Fulvestrant and Dapagliflozin for the Treatment of HR+, HER2 -, PIK3CA Mutant Metastatic Breast Cancer

NCT05025735 | Unknown Phase 2 FDA Drug

• 1 other identifier: CBYL719A0US03T
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a single arm, open label pilot to test the combination of dapagliflozin, a commercially available SGLT-2 inhibitor, in combination with alpelisib + fulvestrant in patients with HR+/HER2- mBC. The objective of this study is to determine if the addition of dapagliflozin to the combination of alpelisib and fulvestrant leads to significant reduction in all-grade hyperglycemia.

Conditions

Metastatic Breast Cancer; HER2-negative Breast Cancer

Keywords

Metastatic Breast Cancer; HER2 Negative; HR Positive

Outcome Measures

Primary Outcomes (1)

• Incidence of all grade hyperglycemia as assessed by CTCAE v5.0

  Through study completion, an average of 1 year.

Secondary Outcomes (3)

• Incidence of Grade 3/4 hyperglycemia as assessed by CTCAE v5.0

  Through study completion, an average of 1 year.

• Overall response rate (ORR) as assed by RECIST 1.1 in patients with measurable disease

  Through study completion, an average of 1 year.

• Progression free survival

  Through study completion, an average of 1 year.

Study Arms (1)

Phase 2 study of Fulvestrant, alpelisib and dapagliflozin

EXPERIMENTAL

A cycle length is defined as 28 days. Fulvestrant 500 mg intramuscular, Cycle 1, Day 1 and Day 15; Cycle 2 and beyond 500 mg Intramuscular Day 1. Alpelisib 300 mg by mouth, daily, continuously beginning on Cycle 1, Day 1. Dapagliflozin 10 mg by mouth, daily, continuously beginning Cycle 1, Day 3.

Drug: Dapagliflozin 10Mg Tab

Interventions

Dapagliflozin 10Mg Tab DRUG

Hyperglycemia is an expected effect of PI3K inhibitors given the pivotal role of PI3K in mediating the response to insulin in multiple tissues. Blocking insulin signaling by p110α inhibitors leads to glycogen breakdown in the liver along with decreased glucose uptake in peripheral tissues. The resulting hyperglycemia causes a compensatory response of increase insulin secretion by the pancreas. If concurrent treatment with dapagliflozin can abrogate the alpelisib induced hyperglycemia and subsequent rebound hyperinsulinemia it may significantly improve the therapeutic efficacy of alpelisib.

Phase 2 study of Fulvestrant, alpelisib and dapagliflozin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \> 18 years old with stage IV or locally advanced, unresectable Stage III breast cancer that is:
• ER and/or PR positive by local laboratory evaluation
• HER2 negative as defined by: either IHC status of 0, 1+ ; IHC of 2+ with FISH negative by ASCO/CAP guidelines.
• If female, post-menopausal status as defined by
• Prior bilateral oophorectomy
• Age \> 60
• Age \<60 and amenorrheic for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene; or ovarian suppression and Follicle-stimulating Hormone (FSH) and estradiol in the postmenopausal range per local normal range.
• Current use of LHRH agonist for ovarian suppression and estradiol and FSH documented in the post-menopausal range.
• PIK3CA activating mutation identified by a either in a CLIA certified tumor genomic assay or ctDNA assay.
• Patients may be:
• relapsed with documented evidence of progression while on (neo) adjuvant endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease
• relapsed with documented evidence of progression more than 12 months following/completion of (neo)adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression while on or after only one line of endocrine therapy for metastatic disease
• newly diagnosed advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine therapy
• Prior endocrine treatment must have included a CDK4/6 inhibitor
• ECOG performance status 0-2

You may not qualify if:

• Patient has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1. Exception to this criterion: patients with any grade of alopecia are allowed to enter the study.
• Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment.
• Patients with Type I diabetes or history of diabetic ketoacidosis
• Patient has received prior treatment with chemotherapy in the metastatic setting, fulvestrant, any PI3K, mTOR or AKT inhibitor
• Patient has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant.
• Patient is concurrently using other anti-cancer therapy.
• Patient has had surgery within 14 days prior to starting study drug or has not recovered from major side effects of surgery.
• Patient has central nervous system (CNS) involvement that does not meet ALL of the following criteria:
• completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 14 days prior to the start of study and
• CNS tumor is clinically stable at the time of screening and
• patient is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases
• Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Patient is following a ketogenic diet and unwilling to change diet.
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study.
• Patient has currently documented pneumonitis (the chest CT scan performed at baseline for the purpose of tumor assessment should be reviewed to confirm that there are no relevant pulmonary complications present).

Sponsors & Collaborators

• Saint Luke's Health System: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Saint Luke's Cancer Institute

Kansas City, Missouri, 64111, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Timothy J Pluard, MD

  Saint Luke's Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelley Aldrich, RN

CONTACT

816-932-2677; slci1research@saint-lukes.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open label pilot to test the combination of dapagliflozin, a commercially available SGLT-2 inhibitor, in combination with alpelisib + fulvestrant in patients with HR+/HER2- mBC.

Study Record Dates

• First Submitted: June 26, 2021
• First Posted: August 27, 2021
• Study Start: August 25, 2021
• Primary Completion: December 1, 2022
• Study Completion: July 1, 2023
• Last Updated: October 19, 2021

Record last verified: 2021-10

Locations

US (1)